1,2-diaryl - 6 - tertiary amino lower-alkoxy-3,4-dihydro naphthalenes



United States Patent 3,476,767 1,2-nrAnYL 6 TERTIARY AMINO LOWER-ALKOXY-3,4-D e a 'IRO NAPHTHALENES William Laszlo Bencze, NewProvidence, N.J., assignor to Ciba Corporation, New York, N.Y., acorporation of Delaware No Drawing. Continuation-impart of applicationSer. No. 494,933, Oct. 11, 1965. This application June 13, 1966, Ser.No. 556,881

int. Cl. C07d 55/00, 31/00, 27/00 US. Cl. 260-3263 3 Claims ABSTRACT OFTHE DISCLOSURE Basically etherified bicyclic phenols having the formulaA=lower aliphatic or araliphatic hydrocarbon radical forming with Ph a 6to 7 membered ring Ph=a 1,2-phenylene N-oxides quarternaries and saltsthereof are hypochloesterolemic agents.

in which Ph stands for a 1,2-phenylene radical and A for a loweraliphatic or araliphatic hydrocarbon radical forming with Ph a 6 to 7membered cycloaliphatic ring containing at most one double bond, theirN-oxides, quaternaries and the salts of these compounds.

The 1,2-phenylene radical Ph, subsituted by the aminoalkoxy group andbeing linked with the divalent hydrocarbon radical A, may beunsubstituted in the remaining three positions or substituted by one ormore than one of the following groups: lower alkyl, such as methyl,ethyl, nor i-propyl, n-, i-, sec. or tert. butyl, lower alkoxy oralkylmercapto, such as methoxy, ethoxy, n-propoxy, methylorethylmercapto, halogen, such as fluoro, chloro or bromo,trifiuoromethyl, nitro or amino, such as dilower alkylamino, e.g.dimethylamino or diethylamino.

An aliphatic hydrocarbon radical A stands for lower alkylene oralkenylene having preferably 4 to 7 carbon atoms, 4 or thereof arering-carbon atoms, such as 1,4- butylene, 1,4- or 1,5-pentylene,2-methyl-1,4butylene, 1,4- 1,5- or 2,5-hexylene, 2-ethyl-1,4-butylene,2,3-dimethyl-1,4-butylene, 2-methyl-l,4- or 1,5-pentylene, 3-methyl-1,5-pentylene, 1,4, 1,5- or 2,5-heptylene, 2,3-dimethyl-1,4 or1,5-pentylene, 2- or 3-methyl-2,5-hexylene or the corresponding alkenylgroups containing the double bond especially between the first andsecond, but also between the second and third ring-carbon atom thereof.These radicals A are preferably unsubstituted, but may also besubstituted, for example by free or esterified hydroxy, such as loweralkanoyloxy or halogen, e.g. acetoxy, propionyloxy, butyryloxy,pivalyloxy, fluoro, chloro or bromo.

An araliphatic radical A is one of the above lower alkylene oralkenylene radicals, which preferably contains one or two monocycli,especially carbocyclic, but also heterocyclic aryl radicals, each boundon one ring-carbon atom of the aliphatic ring. A heterocyclic arylradical is preferably a monoaza or thiacyclic radical, such as 2-, 3- or4-pyridyl, 2- or S-thienyl. These and radicals may 3,476,767 PatentedNov. 4, 1969 be unsubstituted or substituted as shown for the 1,2-phenylene radical Ph.

In the amino-alkoxy radical substituting Ph, the alkylene chainseparates the amino group from the oxygen atom by at least 2 carbonatoms and stands preferably for 1,2-ethylene, 1,2- or 1,3-propylene, butalso for one of the lower alkylene groups shown for A. Its amino groupmay be primary, secondary or preferably tertiary, such as monoordi-lower alkylamino, e.g. methylamino, dimethylamino,N-methyl-N-ethylamino, ethylamino, diethylamino, n-propylamino,di-n-propylamino, ispropylamino, di-isopropylamino, n-butylamino ordi-n-butylamino, cycloalkylamino or N-cycloalkyl-N-lower alkylamino, inwhich cycloalkyl has preferably from five to six ring carbon atoms, e.g.cyclopentylamino, cyclohexylamino, N-cyclopentyl-N-methyl-amino,N-cyclohexyl-N- methyl-amino or N cyclohexyl-N-ethyl-amino, phenylloweralkyl-amino or N-lower alkyl-N-phenyl-lower alkyl amino, e.g.benzylamino, N-benZyl-N-methyl-amino, N- benzyl-N-ethylamino, Nethyl-N-(1-phenylethyl)-amino or N-methyl-N-(2-phenylethyl)-amino,hydroxy-lower alkyl-amino, N (hydroxy-lower alkyl) N lower alkylamino ordi-(hydroxy-lower alkyl)amino, e.g. 2-hydroxyethyl-amino,N-(Z-hydroxyethyl)-N-methylamino or di- (2-hydroxyethyl)-amino, loweralkyleneimino or monoaza-, oxaor thia-alkyleneimino, e.g. pyrrolidino,Z-methyl-pyrrolidino, piperidino, 2- or 4-methyl-piperidino, 3-hydroxy-piperidino, 3-acetoxy-piperidino, 3-hydroxymethyl-piperidino,1,6-hexyleneimino or 1,7-heptyleneimino, piperazino, 4-methyl orethylpiperazino, 4-hydroxyethylor 4-acetoxyethyl-piperazino,3-aZa-1,6-hexyleneimino, 3- methyl 3 aza-l,6-hexyleneimino,4-aza-l,7-heptyleneirnino, 4-methyl-4-aza, 1,7-heptyleneimino,morpholino, 3- methyl-morpholino or thiamorpholino.

In the amino-alkoxy group, the alkyl portion, either partially orintoto, may also form part of a heterocyclic ring system, of which theamino group is a ring member and is separated from the oxygen atom by atleast two carbon atoms. Such amino-alkoxy groups are, for example,piperidyl-(Z) or (3)-rnethoxy, pipen'dyl-(4)-oxy, pyrrolidyl-(3)-oxy,l-methyl-piperidyl-(Z) or (3)-methoxy, l-ethyl-piperidyl-(4)-oxy,1-methyl-pyrrolidyl-(3 )-oxy or imidazolinyl-(2)-methoxy.

The compounds of the invention exhibit valuable pharmacologicalproperties. Primarily they show estrogenic and hypocholesterolemiceffects, as can be demonstrated in animal tests using, for example, ratsas test objects, which are either on a normal or high cholesterol diet.The new compounds are, therefore, useful as estrogens and especiallyhypocholesterolemic agents, for example in the control of fertility,i.e. as anti-fertility agents, or in the treatment of arteriosclerosis.Furthermore, they can be used as intermediates for the preparation ofother use ful products, particularly of pharmacologically activecompounds.

Particularly valuable are compounds of the formula in which each of Rand R stands for hydrogen, phenyl, (lower alkyl)-phenyl, (loweralkoxy)-phenyl, (halogeno) phenyl, (trifiuoromethyl)-phenyl, (di-loweralkylamino)- phenyl, pyridyl, (lower alkyl)-pyridyl, thienyl or (loweralkyl)-thienyl, R for amino, lower alkylamino, di-lower alkylamino,lower alkyleneimino, mono-, aza-, oxaor thia-lower alkyleneimino, n forthe integer 2 or 3, and preferably those in which R and R substitute the1- and 2-positions and the radical O(CH R the 6-position, theirl-dehydro and l-hydroxy derivatives and acid addition salts of thesecompounds.

Especially mentioned is the 1,2-diphenyl-6-(Z-diethylaminoandpyrrolidino-ethoxy)-3,4-dihydro-naphthalene which, when given, forexample, orally in the form of the citrate or hydrochloride at dosesbetween about 0.05 and 20 mg./kg./ day, show outstanding estrogenic andhypocholesterolemic effects.

The compounds of the invention are pre ared according to methods inthemselves known. For example, they are obtained by (a) converting in acompound of the formula in which R is a substituent capable of beingconverted into amino-alkoxy, the substituent R into said aminoalkoxygroup or (b) reducing a compound of the formula A Ph-O-alkyl-amino LHJ Xin which X stands for 0x0 or thiono and, if desired, converting anycompound obtained into another disclosed compound.

In the starting material mentioned under (a) R may be converted intoamino-alkoxy in one step or in stages. A particularly suitable group Ris hydroxy. Usually such phenol, or preferably a salt thereof, isreacted with an amino-alkanol or a reactive ester thereof, especiallythat of a strong mineral acid, such as a hydrohalic acid, e.g.hydrochloric or hydrobromic acid, or that of a strong sulfonic acid,such as a lower alkane or benzene sulfonic acid, e.g. methane or ethanebenzene or p-toluene sulfonic acid.

Another group R is that of the formula O-COY, in which Y representshalogeno or etherified hydroxy. The group Y is particularly lower alkoxyas well as phenoxy. Upon reacting a starting material of which Ph issubstituted by such group R,,, with an amino-alkanol, the desiredcompound can also be formed. The reaction is preferably carried outbetween about 180 and 200.

A further group R is a reactive esterified hydroxyalkoxy group. Here thereactive esterified hydroxy group is primarily halogeno, particularlychloro; it may also be an organic sulfonyloxy group, such as one ofthose mentioned above. A starting material in which R stands forreactive esterified hydroxy-alkoxy is reacted with ammonia or acorresponding primary or secondary amine, to yield the desiredcompounds.

In the starting material mentioned under (b) the group X preferablysubstitutes the ring carbon atom of A which is linked with the1,2-phenylene radical Ph. The reduction of an oxo group X may be carriedout by conventional methods, for example with catalytically activatedhydrogen, with a complex light metal aluminum or bcrohydride, e.g.lithium aluminum hydride or sodium borohydride, or an organic metalcompound, such as a corresponding Grignard compound. With the use of thelatter the group A is converted into another group A depending on thestarting material and the Grignard reagent chosen. A thiono group X maybe reduced, for example with freshly prepared Raney nickel.

The above process is carried out according to methods known per se, inthe presence or absence of diluents, preferably such as are inert to thereagents and are solvents thereof, of catalysts, condensing, salifyingor neutralizing agents and/or inert atmospheres, at low temperatures,room temperature or advantageously elevated temperatures, at atmosphericor superatmospheric pressure.

As noted above, the phenol in reaction (a) is preferably used in theform of a salt thereof. Such salt, for example, a metal salt,particularly an alkali metal, e.g. sodium or potassium salt, is formed,for example, by treatment of the phenol with a metal salt-formingreagent, such as an alkali metal hydride or amide, e.g. sodium hydride,or potassium amide or an alkali metal lower alkoxide, e.g. sodium orpotassium methoxide, ethoxide or tertiary butoxide, an alkali metalcompound of a hydrocarbon, e.g. butyl lithium or phenyl sodium. in casethe phenol is reacted with the amino-alkanol, for example a carbonatemay be used as condensing agent. The latter is, for example, a diarylcarbonate, e.g. diphenyl carbonate or, more particularly, a di-loweralkyl carbonate, e.g. dimethyl carbonate, ethyl methyl carbonate,diethyl carbonate or dibutyl carbonate. The reaction is carried out atan elevated temperature, for example, between about and 210 and, ifdesired, in the presence of a transesterification catalyst enhancing therate of the reaction, e.g. sodium or potassium, sodium or potassiumcarbonate or sodium aluminate, a metal lower alkoxide, e.g. sodiumethoxide or titanium butoxide. The reaction is usually performed in theabsence of an additional diluent. Said transesterification agents mayalso be used with starting materials in which R stands for O-COY.Neutralizing agents are advantageously used together with startingmaterials in which R stands for a reactive esterified hydpoxy-alkoxygroup. They are, for example, alkali metal carbonates or bicarbonates.

A resulting compound may be converted into another disclosed compoundaccording to standard methods. For example, a hydroxy group present in Amay be esterified, for example with the use of a reactive derivative ofa lower alkanoic acid, such as a halide or anhydride thereof, or with ahalogenating agent, such as thionyl chloride o'r phosphorus trichloride.Said hydroxy group present in A, may also be split off, whereby a doublebond is formed. This is easily performed in the case of a tertiaryhydroxy group, for example by pyrolysis or the use of an acid, such ashydrochloric, sulfuric or phosphoric acid. An unsaturated compoundobtained, i.e. such containing a double bond in the ring-moiety A, maybe reduced, for example with nascent or catalytically activatedhydrogen, such as zinc in the presence of an acid, sodium amalgam in thepresence of moist ether or hydrogen in the presence of a platinum,palladium or nickel catalyst.

A tertiary amine obtained may be converted into the N-oxide, forexample, by treating the free base with a suitable N-oxidizing reagent,such as hydrogen peroxide, ozone or persulfuric acid, and in thepresence of a suitable inert diluent. Quaternary ammonium compounds ofthis invention are obtained, for example, by reacting the base with thereactive ester of an alcohol and a strong acid, for example, with alower alkyl halide, di-lower alkyl sulfate, lower alkyl alkaneor benzenesulfonate or phenyl-lower alkyl halide.

The compounds of the invention are obtained in the free form or in theform of their salts, depending on the conditions under which the processis carried out; the salts are also included in the present invention.These are preferably derived from therapeutically useful inorganic ororganic carboxylic or sulfonic acids, such as hydrochloric, hydrobromic,sulfuric or phosphoric acid, acetic, propionic, pivalie, glycolic,lactic, malonic, succinic, maleic, hydroxymaleic, malic, tartaric,citric, benzoic, salicylic, Z-acetoxybenzoic, nicotinic or isonicotinicacid, methane sulfonic, ethane sulfonic, ethane 1,2-disulfonic,2-hydroxyethane sulfonic, p-toluene sulfonic or naphthalene 2-sulfonicacid. Other salts may be useful for purification or characterizationpurposes. Such salts are, for example, those with acidic organic nitrocompounds, e.g. picric, picrolonic or flavianic acid or metal complexacids, e.g. phosphotungstic, phosphomolybdic, chloroplatinic or Reineckeacid. The conversion of the free compounds into the salts or of thesalts into the free compounds or into other salts is achieved accordingto standard procedures, for example with the use of acidic or alkalineagents or ion exchangers.

The invention further includes any variant of the present process inwhich an intermediate obtainable at any stage of the process is used asstarting material and the remaining steps are carried out, or theprocess is discontinued at any stage thereof, or in which the startingmaterials are formed under the reaction conditions, or the reactioncomponents are used in the form of their salts. Mainly, those startingmaterials should be used which lead to those products mentioned in thebeginning as preferred embodiments of the invention.

The starting materials are known or, if they are new, may be prepared bymethods in themselves known. Several starting materials are described incopending applications Ser. Nos. 328,059, filed Dec. 4, 1963, now PatentNo. 3,238,218; 411,632, filed Nov. 16, 1964 and 481,954, filed Aug. 23,1965, now abandoned, or may be prepared analogous to the proceduresdescribed therein.

The compounds of the invention as well as the corresponding startingmaterials may be in the form of pure geometric or optical isomers or inthe form of mixtures thereof. Such mixtures may be separated accordingto known methods, diastereoisomers or cis-trans isomers, for example, byfractional crystallization or chromatography and racemates by conversioninto appropriate diastereoisomers.

The compounds of the invention may be used in the form of pharmaceuticalcompositions which are a further object of the present invention. Theycontain said compounds in admixture with a pharmaceutically acceptable,organic or inorganic, solid or liquid carrier, which usually representsthe major portion by weight of such compositions. The compositions arein solid form, for example, as capsules, tablets or dragees, in liquidform, for example as solutions or suspensions. Suitable carriermaterials are, for example, starches, e.g. corn, wheat or rice starch,sugars, e.g. lactose, glucose or sucrose, stearic acid or salts thereof,e.g. magnesium or calcium stearate, stearyl alcohol, talc, gums, acacia,tragaca'nth, propylene glycol or polyalkylene glycols. The quantity andthe nature of the carrier ingredients can vary widely and depend, interalia, upon the desired physical appearance or size of the composition ormethod of manufacture. If necessary, the compositions may contain otherauxiliary substances, such as preserving, stabilizing, wetting oremulsifying agents, salts for varying the osmotic pressure or buffers.They may also contain, in combination, other pharmacologically usefulsubstances.

The following examples illustrate the invention, temperatures are givenin degrees centigrade and all parts wherever given are parts by weight.

EXAMPLE 1 To the stirred solution containing 1.7 g. 1,2-diphenyl-6-hydroxy-3,4-dihydro-naphthalene in ml. dimethylformamide, cooled in anice bath, 0.274 g. of a 56% sodium hydride suspension in mineral oil areadded in portions. After the hydrogen evolution has ceased 0.773 g.2-dimethylamino-ethyl chloride in 15 ml. toluene are slowly added andthe mixture is stirred at room temperature for 5 hours. It is thenfiltered, the residue washed with diethyl ether, the filtrate evaporatedunder reduced pressure, the residue mixed with water and extracted withdiethyl ether. The organic layer is shaken with 2 N hydrochloric acid,the aqueous layer neutralized with ammonia and extracted with diethylether. The extract is washed with brine, dried, filtered and evaporatedin vacuo to yield a brown oil. This is dissolved in methyl-ethylketoneand the solution of 2.3 g. anhydrous citric acid in boilingmethylethylketone is added. The crystals formed are filtered off andrecrystallized from methyl-ethylketonediethyl ether to yield the1,2-diphenyl-6-(Z-diethylaminoethoxy)-3,4-dihydro-naphthalene citrate ofthe formula melting at 164166.

The starting material is prepared as follows: To the Grignard reagent,prepared from 4.8 g. magnesium, 31.4 g. bromobenzene, 300 ml. diethylether and a few drops methyl iodide and cooled in an ice bath, 25.2 g.2-phenyl- 6-methoxy-tetralone in 300 ml. benzene are added slowly andthe mixture is refluxed for 5 hours. Hereupon it is poured onto ice andconcentrated hydrochloric acid, extracted with diethyl ether, theextract washed with water and brine, dried, filtered, and evaporated invacuo. The residue is refluxed for one hour in 300 ml. concentratedhydrochloric acid, which is then diluted with water, extracted withdiethyl ether, the extract Washed with water and brine, dried, filteredand evaporated to yield the 1,2-diphenyl-6-methoxy-3,4-dihydronaphthalene which melts afterrecrystallization from aqueous ethanol at 98-101.

4.0 g. thereof are heated in a melt of pyridine hydrochloride for 30minutes at 250. The melt was prepared by evaporating the mixture of 39.2ml. concentrated hydrochloric acid and 35.8 g. pyridine until the vaporreached a temperature of about 250. The mixture is then poured onto ice,extracted with diethyl ether, the extract washed with water and brine,dried, filtered and evaporated in vacuo. The residual orange oil isdistilled and the fraction boiling at 205 0.2 ml. collected; itrepresents the 1,2 diphenyl 6 hydroxy 3,4 dihydronaphthalene.

EXAMPLE 2 To the Grignard reagent, prepared from 0.47 g. magnesium and3.4 g. 4-methyl-bromobenzene in 25 ml. diethyl ether, 3.7 g.2-(4-chloro-phenyl)-6-(2-diethylaminoethoxy)-tetralone in 25 ml. benzeneare added dropwise with stirring at 10. The mixture is stirred for 30minutes at room temperature, refluxed for 2 hours and allowed to standovernight at room temperature. The next day it is refluxed for 3additional hours, then cooled in an ice bath and concentrated, aqueousammonium chloride solution is added dropwise while stirring. The mixtureis extracted with ethyl acetate, the organic layer washed with brine,dried, filtered, evaporated under reduced pressure and the residuerecrystallized from diethyl ether-pentane to yield the 1 hydroxy l (4methyl phenyl) 2 (4- chloro phenyl) 6 (2 diethylamino ethoxy) 1,2,3,4-tetrahydronaphthalene of the formula melting at 122124. This compound isdissolved in benzene, chromatographed on 30 g. alumina (neutral,activity III) and the benzene eluate recrystallized from aqueous ethanolto yield a somewhat purer product melting at 127-128".

The starting material is prepared as follows: 16.0 g. 2 (4 chlorophenyl) 6 methoxy tetralone are refluxed in the mixture of 220 ml.acetic acid and 220 ml.

48% hydrobromic acid for 6 hours. It is then evaporated in vacuo, theresidue mixed with water, the crystals formed filtered off and dried toyield the 2-(4-chloro-phenyl)-6- hyrdoxy-tetralone melting at 187-196;it is used without further purification.

14.5 g. thereof are dissolved in 32 ml. dimethylformamide and, whilestirring, 2.42 g. of a 53% suspension of sodium hydride in mineral oilare added in small portions. After the hydrogen evolution has ceased,the reaction mixture is cooled and 6.97 g. Z-diethyIamino-ethyl chloridein 31.2 ml. toluene are added. The whole is refluxed for 3 hours,allowed to cool to room temperature, filtered, the residue Washed withbenzene and diethyl ether, the filtrate evaporated in vacuo, the residuemixed with water and extracted with diethyl ether. The organic layer isshaken with 2 N hydrochloric acid, the aqueous layer made basic withammonia, extracted with diethyl ether,

the extract washed with water and brine, dried, filtered and evaporated.The residual oil crystallizes upon cooling and is recrystallized fromaqueous ethanol to yield the 2 (4 chloro phenyl) 6 (2diethylaminoethoxy)-tetralone melting at 7273.

EXAMPLE 3 In the analogous manner described in the previous examples thefollowing compounds can be prepared by using the equivalent amounts ofthe corresponding starting materials: 5 (2 dimethylamino ethoxy) 1,2,3,4tetrahydro naphthalene, 2 (4 pyridyl) 6 (3 dimethylamino propoxy)1,2,3,4 tetrahydro naphthalene, 1- (4 methoxy phenyl) 2 phenyl 6 (2pyrrolidinoethoxy) 1,2,3,4 tetrahydro naphthalene, 1,2 diphenyl 6 [2 (4methyl piperazino) ethoxy] benzsuberane, 1 (4 trifiuoromethyl phenyl) 2(4 dimethylamino phenyl) 7 (2 morpholino ethoxy)- 3,4 dihydronaphthalene, 1 (3,5 dimethoxy phenyl) 2 (3 thienyl) 6 (2 tert.butylamino ethoxy)- 3,4 dihydronaphthalene, 1 hydroxy 1 phenyl 2- (4methyl phenyl) 6 (4 amino butoxy) 1,2,31,4- tetrahydronaphthalene, 3 (4chloro phenyl) 6 (2- diethylamino ethoxy) benzsuberane or 1 phenyl 2-methyl 2 (4 methylmercapto phenyl) 8 (3- piperidino-propoxy)-1,2,3,4-tetrahydronaphthalene.

EXAMPLE 4 Preparation of 160,000 tablets each containing 0.025 g. of theactive ingredient.

Ingredients:

G. 1,2-diphenyl-6-(2-diethylamino-ethoxy)- 3,4-dihydronaphthalenecitrate 4,000.0 Lactose 28,2890 Corn starch 3,410.0 Confectioners sugar2,800.0 Colloidal silica 1,000.0 Stearic acid powder 400.0 Calciumstearate 100.0 Color FD&C Yellow No. 5 1.0

Purified Water q.s.

Procedure The citrate, the lactose, 2,500.0 g. of the corn starch,

the confectioners sugar and the colloidal silica are passed through aNo. 16 screen into a mixer and blended at low speed for twenty minutes.The remainder of the corn starch is suspended in a cold solution of thecolor in 1,000 ml. of purified water, and a paste is formed by graduallyadding 4,000 ml. of boiling purified water. The mixed powders aregranulated with the above paste, using additional water as required.

The resulting moist mass is passed through a mill, using a No. 4Ascreen, placed on trays and dried at 38 C. un-

til the moisture content is between 2 percent and 3 percent. Thegranules are broken on a mill through a No. 16 screen, and treated withthe stearic acid and the calcium stearate, both screened through a No.20 screen. After mixing for twenty minutes, the granulation iscompressed into tablets, each weighing 0.25 g., using inch dies,standard concave punches, uppers bisected, lowers monogrammed.

EXAMPLE 5 To the mixture of 5.2 g. 1,2-diphenyl-6-hydroxy-3,4-dihydro-naphthalene and 50 ml. dimethylformamide, cooled in an ice bath,0.836 g. of a 56% sodium hydride suspension in mineral oil are addedwhile stirring. The ice bath is removed and the mixture is stirred untilthe hydrogen evolution ceases. The solution is again cooled and 2.8 g.2-pyrrolidino-ethyl chloride in 50 ml. toluene are added. Aftercompleted addition the mixture is stirred at room temperature for 5hours, then filtered and the filtrate evaporated in vacuo. To theresidue water is added 8 and the solid filtered olf. It is dissolved indiethyl ether, the solution washed with water and brine, filtered andevaporated. The residue is again dissolved in diethyl ether and thesolution acidified with etheral hydrochloric acid. After cooling theprecipitate formed is separated and recrystallized from acetone to yieldthe 1,2-diphenyl- 6-(2 pyrrolidino-ethoxy)-3,4-dihydro-naphthalenehyrochloride of the formula \/O-C H4N melting at ZOO-201.

EXAMPLE 6 melting at -108.

From the mother liquor an oil is isloated upon evaporation, which issalified with citric acid to yield the 1,2-diphenyl 6-(2-diethylamino-ethoxy)-3,4-dihydro-naphthalene citrate monohydrate,melting at 142-145 it corresponds to the compound obtained according toExample 1.

What is claimed is:

1. A compound having the formula in which each of R and R stands for amember selected from the group consisting of phenyl, (lower alkyl)-phenyl, (lower alkoxy)-phenyl, (halogeno)-phenyl,(trifluoromethyl)-phenyl, (di-lower alkylamino)-phenyl, pyridyl, (loweralkyl)-pyridyl, thienyl and (lower alkyl)- thienyl, wherein lower alkylor lower alkoxy have 1 to 4 carbon atoms, R for a member selected fromthe group consisting of di-lower alkylamino having a total of 2 to 8carbon atoms, lower alkyleneimino having 4 to 7 carbon atoms,pyrrolidino, Z-methyl-pyrrolidino, piperidino, 2- or4-methyl-piperidino, 3-hydroxy piperidino, S-acetoxy-piperidino,3-hydroxymethyl-piperidino, 1,6-hexyleneimino or 1,7-heptyleneimino,piperazino, 4-methyl or ethyl-piperazino, 4-hydroxy ethyl or4-acetoxyethyl-piperazino, 3-aza-l,6-hexyleneimino, 3-methyl-3-aza-l,6hexyleneimino, 4-aza-1,7-heptyleneimino, 4-methyl 4aza-1,7-heptyleneimino, morpholino, 3-methyl-morpholino orthiamorpholino, n for an integer from 2 to 3 or a therapeuticallyacceptable acid addition salt thereof.

2. A compuond as claimed in claim 1 and being the1,2-dipheny1-6-(Z-diethylamino-ethoxy) 3,4 dihydronaphthalene or atherapeutically acceptable acid addition salt thereof.

9 3. A compound as claimed in claim 1 and being the 1,2-diphenyl 6(2-pyrrolidino-ethoxy)-3,4-dihydr0- naphthalene or a therapeuticallyacceptable acid addition salt thereof.

References Cited UNITED STATES PATENTS 3,320,271 5/1967 Lednicer 260-30710 ALEX MAZEL, Primary Examiner I. TOVAR, Assistant Examiner US. Cl.X.R.

